the dosing regimen of pyrotinib in her2-positive advanced first-line breast cancer: a phase i clinical study

Conditions: Breast Cancer

Summary: evaluate the safety and efficacy of pyrotinib at different doses in combination with trastuzumab and paclitaxel chemotherapy for first-line treatment of her2-positive advanced breast cancer.

this study is planned to include 200 patients with her2-positive advanced breast cancer meeting the admission criteria between 2024-11-01 and 2026-11-01. statistical software will be used by the randomization officers for 1:1 allocation to pyrotinib 320mg in combination with trastuzumab and paclitaxel chemotherapy group and pyrotinib 400mg in combination with trastuzumab and paclitaxel chemotherapy group.

Eligibility criteria:
inclusion criteria: * the subjects voluntarily joins the study and signs the informed consent; * subject is an adult female or male ≥ 18 years old and ≤ 75 years old at the time of informed consent; * her2-positive advanced breast cancer confirmed by pathology:her2-positive was defined as \>10% of immunoreactive cells with an immunohistochemical (ihc) score of 3+ or her2 gene amplification as a result of in situ hybridization (ish). her2 positivity should be verified by the pathology department of the research center; * recurrent or metastatic breast cancer; patients with local recurrence had to be confirmed by the investigator as not amenable to curative resection; * at least one measurable lesion or only bone metastases according to recist v1.1 criteria (including osteolytic lesions or mixed osteolytic/osteoblastic lesions); * when randomized, eastern cooperative oncology group(ecgo) physical fitness status is 0 or 1 point; * vital organ function meets the following requirements (excluding the use of any blood components and cell growth factors during screening) : absolute neutrophil (anc) count ≥1.5×109/l; platelet (plt) ≥100×109/l; hemoglobin (hb) ≥9g/dl; total bilirubin(tbil) ≤uln((known patients with gilbert's syndrome:total bilirubin(tbil) ≤2×uln);alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤1.5×uln(patients with liver metastasis:alt and ast≤5×uln); alkaline phosphatase (akp) ≤ 2.5 times uln; blood urea nitrogen and serum creatinine (cr) ≤1.5×uln;left ventricular ejection fractions(lvef)≥50%;corrected qt interval(qtcf)\<470msec. exclusion criteria: * the patient has received any systemic antitumor therapy at the stage of recurrence/metastasis, including any agents targeting egfr or her2, systemic chemotherapy, immunotherapy, and more than first-line endocrine therapy, as well as other antitumor therapies deemed by the investigators to be excluded; * tyrosine kinase inhibitor (tki) preparations or macromolecular antibodies against her have been used at any stage of breast cancer, except for trastuzumab in the (new) adjuvant stage; * in the stage of breast cancer (new) adjuvant therapy, the time interval from the end of systemic therapy (except endocrine therapy) to the discovery of recurrence/metastasis is \<12 months; * patients with active brain metastases with pial metastases confirmed by mri or lumbar puncture (brain metastases requiring mannitol treatment or with symptoms); * grade≥ 3 peripheral neuropathy according to ctcae4.0.3 criteria; * patients judged by the investigators to be unsuitable for systematic chemotherapy; * use of endocrine therapy drugs within 7 days prior to randomization; * patients with other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or squamous cell carcinoma (patients with other malignancies occurring more than 5 years after randomization, such as those cured only by surgery, are allowed to be included); * had a major surgical procedure or significant trauma within 4 weeks prior to randomization, or was expected to undergo major surgery; * serious heart disease or discomfort, including but not limited to the following: previous history of heart failure or systolic dysfunction (lvef\ 150mmhg and/or diastolic blood pressure \>100mmhg); * inability to swallow, chronic diarrhea, intestinal obstruction, or other factors affecting the administration and absorption of medications; * known allergic history of the drug components of this protocol; * a history of immunodeficiency, including hiv infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; * presence of third-space fluid accumulation that cannot be controlled by drainage or other methods (e.g., pleural fluid and ascites); * pregnant and lactating female subjects, or fertile subjects who were unwilling to use effective contraception throughout the trial period and within 3 months after the last study dose; * have a serious concomitant disease or other co-medical condition that interferes with planned treatment or any other condition that is not suitable for participation in this study, such as active hepatitis b, a lung infection requiring treatment.

Keywords: her2 positive pyrotinib